Search Results (166)

Primary hyperoxalurias (PHs) are rare autosomal recessive disorders characterized by overproduction of oxalate, a metabolic end product that readily forms calcium oxalate crystals. Excess hepatic oxalate leads to recurrent kidney stones, nephrocalcinosis, and progressive renal injury, often culminating in end-stage kidney disease (ESKD). Once renal clearance declines, systemic oxalate accumulation can cause multisystem deposition. PH encompasses three types—PH1, PH2, and PH3—caused by deficiencies in the hepatic enzymes AGT, GRHPR, and HOGA1, respectively, resulting in accumulation of glyoxylate and subsequent oxalate overproduction. Clinical presentation varies from infantile oxalosis to adult-onset recurrent nephrolithiasis, with PH1 generally being the most severe. Diagnosis relies on urinary oxalate measurements, plasma oxalate in advanced chronic kidney disease, urinary metabolite profiling, imaging, and genetic testing. Management includes hyperhydration, citrate supplementation, pyridoxine for responsive PH1 patients, dialysis and transplantation when required, while RNA interference therapies targeting glycolate oxidase or LDHA have demonstrated substantial biochemical efficacy in PH1 and represent promising emerging therapeutic options, although long-term clinical outcome data remain limited and broader applicability to other PH types is still under investigation. Future strategies focus on modulating intestinal oxalate absorption, gut microbiome therapies, oxalate-degrading enzymes, and novel gene-editing approaches. Early diagnosis and individualized management are critical to prevent kidney injury and systemic oxalosis. In this review, we summarize the genetic, biochemical, and clinical features of PH and discuss current and emerging therapeutic strategies. Full article

The integration of omics technologies, including genomics, proteomics, metabolomics, and microbiomics, has transformed sports science, particularly soccer, by providing new opportunities to optimize player performance, reduce injury risk, and enhance recovery. This systematic literature review was conducted in accordance with PRISMA 2020 guidelines and structured using the PICOS/PECOS framework. Comprehensive searches were performed in PubMed, Scopus, and Web of Science up to August 2025. Eligible studies were peer-reviewed original research involving professional or elite soccer players that applied at least one omics approach to outcomes related to performance, health, recovery, or injury prevention. Reviews, conference abstracts, editorials, and studies not involving soccer or omics technologies were excluded. A total of 139 studies met the inclusion criteria. Across the included studies, a total of 19,449 participants were analyzed. Genomic investigations identified numerous single-nucleotide polymorphisms (SNPs) spanning key biological pathways. Cardiovascular and vascular genes (e.g., ACE, AGT, NOS3, VEGF, ADRA2A, ADRB1–3) were associated with endurance, cardiovascular regulation, and recovery. Genes related to muscle structure, metabolism, and hypertrophy (e.g., ACTN3, CKM, MLCK, TRIM63, TTN-AS1, HIF1A, MSTN, MCT1, AMPD1) were linked to sprint performance, metabolic efficiency, and muscle injury susceptibility. Neurotransmission-related genes (BDNF, COMT, DRD1–3, DBH, SLC6A4, HTR2A, APOE) influenced motivation, fatigue, cognitive performance, and brain injury recovery. Connective tissue and extracellular matrix genes (COL1A1, COL1A2, COL2A1, COL5A1, COL12A1, COL22A1, ELN, EMILIN1, TNC, MMP3, GEFT, LIF, HGF) were implicated in ligament, tendon, and muscle injury risk. Energy metabolism and mitochondrial function genes (PPARA, PPARG, PPARD, PPARGC1A, UCP1–3, FTO, TFAM) shaped endurance capacity, substrate utilization, and body composition. Oxidative stress and detoxification pathways (GSTM1, GSTP1, GSTT1, NRF2) influenced recovery and resilience, while bone-related variants (VDR, P2RX7, RANK/RANKL/OPG) were associated with bone density and remodeling. Beyond genomics, proteomics identified markers of muscle damage and repair, metabolomics characterized fatigue- and energy-related signatures, and microbiomics revealed links between gut microbial diversity, recovery, and physiological resilience. Evidence from omics research in soccer supports the potential for individualized approaches to training, nutrition, recovery, and injury prevention. By integrating genomics, proteomics, metabolomics, and microbiomics data, clubs and sports practitioners may design precision strategies tailored to each player’s biological profile. Future research should expand on multi-omics integration, explore gene–environment interactions, and improve representation across sexes, age groups, and competitive levels to advance precision sports medicine in soccer. Full article

Vasculitides are a heterogeneous group of disorders characterized by inflammation of blood vessel walls, leading to tissue ischemia and organ injury. Traditional inflammatory markers such as the erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) are widely used but lack diagnostic specificity. This has driven the search for more informative biomarkers across vasculitis subtypes. This review summarizes current evidence for validated and emerging biomarkers in large-, medium-, small-, and variable-vessel vasculitis, as well as single-organ vasculitis. Key analytes reflect systemic inflammation, such as serum amyloid A (SAA) and interleukin-6 (IL-6), as well as endothelial activation, complement pathways, neutrophil and macrophage activation, and organ-specific damage. Promising candidates include pentraxin-3 (PTX3) and matrix metalloproteinase-9 (MMP-9) in large-vessel vasculitis; N-terminal pro-B-type natriuretic peptide (NT-proBNP) and S100 proteins in Kawasaki disease; galactose-deficient immunoglobulin A1 (Gd-IgA1) and urinary angiotensinogen (AGT) in IgA vasculitis; and tissue inhibitor of metalloproteinases-1 (TIMP-1), S100 proteins, complement C3, and PTX3 in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis. Although these biomarkers provide mechanistic insight, most lack disease-specificity, external validation, or standardized assays. Future progress will require multicenter studies, harmonized testing, and integrated biomarker panels combined with imaging modalities to improve diagnosis, activity assessment, and monitoring. Full article

Introduction: The aim of this study was to determine the position of otoconial debris in lateral ampullar or non-ampullar canalolithiasis, based on two parameters: (1) the direction of the nystagmus appearing when the patient lies down, if present, and (2) the positional nystagmus evoked by the supine roll test. Methods: Theoretical results were compared with a population of 170 patients observed over the past ten years for horizontal canal benign paroxysmal positional vertigo (HC-BPPV). The series included 141 geotropic and 29 apogeotropic cases. Results: Among the geotropic forms, 80 showed no supine nystagmus (Geotropic Nystagmus with no supine nystagmus, GT0) (56.7%), 51 had supine nystagmus directed toward the healthy side (Geotropic Nystagmus with supine nystagmus congruent, direct toward the healthy side, GT+) (36.2%), and 10 toward the affected side (Geotropic Nystagmus with supine nystagmus incongruent direct to the affected side, GT−) (7.1%). In the apogeotropic group, 10 showed no supine nystagmus (Apogeotropic nystagmus with no supine nystagmus, AGT0) (34.6%), 16 had nystagmus toward the affected side (Apogeotropic Nystagmus with supine nystagmus congruent, direct toward the affected side, AGT+) (55.2%), and 1 toward the healthy side (Apogeotropic Nystagmus with supine nystagmus Incongruent, direct toward the healthy side, AGT−) (3.4%). Two cases presented monopositional apogeotropic nystagmus (mAGT), consistent with a “sieve-type canal jam” (6.8%). Overall, 90 out of 170 patients (52.9%) showed no nystagmus in the supine position, with a statistically significant difference between variants (p = 0.0474, Yates correction). Conclusions: The comparison between lying-down nystagmus and positional nystagmus, assessed through the Supine Roll Test as the leading diagnostic maneuver for horizontal canal involvement, may help identify the initial location of debris within the lateral semicircular canal and guide the appropriate liberatory maneuver, while the effectiveness and side of the maneuver allow the distinction between canal-side and utricular-side jams. Full article

Background: Recurrent pregnancy loss (RPL) is a multifactorial condition in which genetic variants associated with thrombophilia may contribute to altered coagulation and adverse pregnancy outcomes. Objective: This study aimed to investigate the association between thrombophilia-related single nucleotide variants (SNVs) and coagulation-related metabolites in a cohort of Mexican women with RPL. Methods: A retrospective and descriptive design was conducted including 105 women with at least two consecutive miscarriages and with a multidisciplinary approach that included a thrombophilia-associated SNVs panel. Peripheral blood samples were collected after fasting for biochemical and molecular analyses. Genotyping of thrombophilia-associated SNVs was performed using real-time PCR with custom-designed TaqMan probes on a Rotor-Gene Q platform, including variants in AGT (rs4762, rs699), F7 (rs6046), FGB (rs1800790), MTR (rs1805087), MTRR (rs1801394), MTHFR (rs1801133, rs1801131), F2 (rs1799963), F5 (rs6025), SERPINE1 (rs1799889), F12 (rs1801020), and F13A1 (rs5985) genes. Coagulation parameters evaluated were folic acid, cobalamin, fibrinogen, D-dimer, homocysteine, antithrombin III activity, thrombin time (TT), prothrombin time (PT), activated partial thromboplastin time (aPTT), international normalized ratio (INR), and Factor XII activity. Results: Significant differences were found in INR values across F7-rs6046 genotypes (p = 0.006), with an additive model showing a mean difference of 0.05 (p = 0.0009). The F12-rs1801020 variant was strongly associated with Factor XII activity (p = 0.002) and aPTT (p = 0.045). Conclusions: These findings indicate that F7-rs6046 and F12-rs1801020 genotypes influence specific coagulation parameters, suggesting that certain thrombophilia-associated SNVs may modulate the hemostatic profile in Mexican women with RPL and contribute to personalized risk assessment in reproductive medicine. Full article

Background/Objectives: Pathogenic variants in the GBA1 gene, which encodes the lysosomal enzyme $\beta$-glucocerebrosidase, cause Gaucher disease (GD) and represent one of the strongest genetic risk factors for Parkinson’s disease (PD). However, not all carriers develop PD, suggesting the involvement of additional modifiers. Transcriptomic alterations shared between GD and PD may reveal such modifiers and provide insights into the mechanisms linking GBA1 to PD. Methods: Eighteen transcriptomic datasets spanning GD, GBA1-associated PD, and sporadic PD were integrated to identify shared, directionally concordant differentially expressed genes, followed by pathway enrichment analysis. Causal relationships were assessed using two-sample Mendelian randomisation with whole-blood and brain genetic instruments and PD GWAS summary statistics. Diagnostic relevance was evaluated in independent datasets using machine learning, while metabolic implications were explored with a neuron-specific genome-scale metabolic model. Results: Shared DEGs were enriched in lysosomal, lipid, redox, and endocrine pathways. Mendelian randomisation prioritised 12 risk genes in whole blood and 5 in brain tissue, with 4 overlapping; risk-increasing effects were observed for GPNMB, MMP9, TRIM22, TESMIN, NFE2L3, FAM89A, METTL7A, PID1, NECAB2, and LPL, whereas GIPR and RASGRF2 showed protective effects, and AGT was brain-specific. Diagnostic signals were concentrated in a subset of genes, while metabolic modelling revealed convergent but subtype-specific perturbations across metabolic circuits. Conclusions: Convergent genetic, transcriptomic, and metabolic evidence supports at least two mechanistic routes to PD risk: a GBA1-sensitised lysosomal–lipid/redox axis, and a GBA1-independent neuronal–endocrine axis. These findings explain the variable risk among GBA1 carriers, identify candidate biomarkers, and highlight pathway-anchored targets for stratified intervention. Full article

Endometrial cancers increase expression of the renin–angiotensin system (RAS). This study aimed to determine if inhibiting the RAS would reduce the viability and proliferation of endometrial cancer cells. The expression of RAS genes was measured in three endometrial epithelial adenocarcinoma cell lines (Ishikawa, HEC-1-A, AN3CA). Ishikawa cells had the highest expression of REN, ACE, and AGTR1 mRNA. AGT mRNA and protein levels were most abundant in HEC-1-A cells. We then determined the effects of drugs that inhibit the action of renin (VTP-27999 and aliskiren) or angiotensin-converting enzyme (perindoprilat) or block the angiotensin II type 1 receptor (losartan and telmisartan). Overall, VTP-27999, aliskiren, perindoprilat, and losartan had minimal effects on cell viability in all three cell lines, and combinations of these drugs did not have any effect. Telmisartan (a dual angiotensin receptor blocker and PPAR-γ agonist) significantly reduced the viability of all three cell lines and reduced the proliferation of both Ishikawa and AN3CA cells. Telmisartan was more effective than troglitazone (PPAR-γ agonist) in Ishikawa and HEC-1-A cells. RAS inhibitors were most effective in Ishikawa cells, which had the highest levels of RAS expression. Therefore, levels of RAS expression in endometrial cancers might indicate the potential efficacy of RAS drugs. Full article

Athletic performance results from complex interactions between genetic and environmental factors. This review compiles and synthesizes available literature on polymorphic genes associated with endurance, power, and strength performance, as well as their links to injury susceptibility and chronic metabolic diseases. Endurance performance is modulated by ACE, PPARGC1A, HFE, UCP2, UCP3, CDKN1A, and PPARA, regulating mitochondrial biogenesis, oxygen utilization, and muscle fiber composition. Power performance involves ACTN3, MCT1, IGF1, AMPD1, AGT, and AGTR2, affecting anaerobic metabolism, lactate clearance, and fast-twitch fiber recruitment. Strength performance is influenced by AR, PPARG, ARK2N, MMS22L, LRPPRC, PHACTR1, and MTHFR, related to androgen signaling, muscle hypertrophy, and recovery. Injury-related genes (COL1A1, COL5A1, IL6, VEGFA, NOG) and metabolic risk genes (FTO, PPARG, ADRB3) further highlight the clinical relevance of genomics. Collectively, these insights support the application of genetic information to personalize training, enhance performance, prevent injuries, and guide exercise interventions to mitigate metabolic disease risk. Full article

This study investigates the mechanical properties of titanium (Titanflex®) and cobalt-chromium (Co-Cr) alloys for potential use in removable denture bases. Titanium alloys have gained attention due to their biocompatibility and regulatory concerns surrounding Co-Cr, which has been classified as a carcinogenic, mutagenic, and toxic to reproduction (CMR) substance under EU MDR (2017/745). Using selective laser melting (SLM), test specimens of Titanflex® and Co-Cr alloys were 3D-printed at different angles (0°, 45°, 90°) and compared to conventionally cast Co-Cr samples. Tensile testing was conducted to assess modulus of elasticity (E), proof stress (Rp_0.2), ultimate tensile strength (Rm), elongation parameters (Ag, Agt, At), and maximum load (Fm). Results showed that Titanflex® printed at 45° (Ti45) exhibited the highest Rp_0.2, Rm, and Fm, indicating superior strength and plastic resistance. Ti0 displayed the greatest elongation properties, highlighting titanium’s ductility. Co-Cr alloys demonstrated higher stiffness but lower ductility. Printing orientation significantly influenced mechanical properties, particularly in 3D-printed samples. Overall, Ti45 presented a balanced profile of strength and flexibility, making it a promising candidate for denture bases, while Co-Cr remains a rigid alternative with established clinical use. Future research should explore long-term performance under functional and biological conditions to guide clinical application. Full article

Background/Objectives: This systematic review aimed to gather the most recent evidence regarding the link between genetic polymorphisms and physical performance in team sports, with a focus on the practical utility of this information for athlete selection, training personalization, and injury prevention. Methods: Sixteen studies published between 2018 and 2025 were analyzed and selected from six international databases, in accordance with the PRISMA guideline. Only English-language studies were included, which evaluated active athletes in team sports and investigated associations between genetic variations, such as Actinin Alpha 3 (ACTN3 R577X), Angiotensin I Converting Enzyme (ACE I/D), Peroxisome Proliferator-Activated Receptor Alpha (PPARA), Interleukin 6 (IL6), and Nitric Oxide Synthase 3 (NOS3), and physical performance parameters. The methodological quality of the studies was assessed using the Q-Genie tool, with all studies scoring over 45 across all 11 items, indicating high quality. Results: The ACTN3 and ACE genes stood out due to their consistent association with traits such as strength, speed, endurance, and recovery capacity. Other genes, such as PPARA, Fatty Acid Amide Hydrolase (FAAH), Angiotensinogen (AGT), and NOS3, complemented this genetic profile by being involved in the regulation of energy metabolism and injury predisposition. An increasing number of studies have begun to adopt cumulative genotype scores, suggesting a shift from a monogenic approach to complex predictive models. Conclusions: The integration of genetic profiling into the evaluation and management of athletes in team sports is becoming increasingly relevant. Although current evidence supports the applicability of these markers, robust future research conducted under standardized conditions is necessary to validate their use in sports practice and to ensure sound ethical standards. Full article

The decarbonization and automation of port operations are emerging as key strategies to enhance the sustainability and efficiency of maritime logistics. This study proposes a simulation-based framework to assess the operational and environmental impacts of transitioning from traditional Internal Combustion Engine (ICE) tractors to Battery Electric Tractors (BET) and Automated Electric Guided Tractors (e-AGT) in Roll-on/Roll-off (Ro–Ro) port terminal operations. The proposed framework is applied to simulate a full vessel turnaround at the Ro–Ro terminal of the Port of Ravenna (Italy). A set of Key Performance Indicators (KPIs) is defined to evaluate turnaround time, vehicle productivity, energy consumption and CO₂ emissions across three scenarios. The results indicate that both BET and e-AGT configurations significantly reduce emissions compared to ICE, with reductions up to 40%. However, the e-AGT scenario reveals operational drawbacks, including increased unloading time and reduced fleet availability due to charging constraints and routing limitations. These findings highlight the environmental potential of automation and electrification but also emphasize the need for integrated planning of fleet size, charging infrastructure and circulation specifications. The proposed framework provides a replicable decision-support tool for port authorities and logistics operators to evaluate alternative handling technologies under realistic conditions. Full article

The study examined the association between body composition and beverage consumption and the risk of asthma and chronic obstructive pulmonary disease (COPD) and explored the single nucleotide polymorphisms (SNPs) involved in these associations by leveraging summary statistics from genome-wide association studies (GWAS) in nonoverlapping populations. The IEU OpenGWAS project was sourced for exposure datasets: body mass index, body fat percentage, fat-free mass, total body water mass, alcohol intake frequency, and coffee intake, and selected health outcome datasets: asthma and chronic obstructive pulmonary disease. Datasets were assessed and filtered using R, followed by a two-sample Mendelian randomization analysis. The MR Egger, weighted median, inverse variance weighted, simple mode, and weighted mode methods were used to examine the association between exposures and outcomes. Heterogeneity and pleiotropy analyses were used to evaluate the reliability of results. Additionally, SNPnexus was used to ascertain SNPs linked to established phenotypes, while SNP annotation was obtained from the Ensembl BioMart database via the biomaRt package. Genes belonging to overlapping groups were visualized using ComplexHeatmap. Higher body fat percentage (OR = 1.72, 95% CI: 1.23–2.41, p = 0.002), increased BMI (OR = 1.56, CI: 1.23–1.20, p = 2.53 × 10⁻⁴), and more frequent alcohol intake (OR = 1.34, CI: 1.08–1.68, p = 0.009) were associated with elevated COPD risk. Asthma risk was similarly increased with higher body fat percentage (OR = 1.60, CI: 1.23–2.21, p = 0.001), BMI (OR = 1.54, CI: 1.29–1.84, p = 2.23 × 10⁻⁶), fat-free mass (OR = 1.21, CI: 1.02–1.44, p = 0.032), and alcohol intake frequency (OR = 1.19, CI: 1.01–1.40, p = 0.039). Total body water mass and coffee intake were not associated with asthma and COPD. SNP annotation revealed that some genetic variants that influenced the association of the exposure variables with asthma and COPD were missense variants in several genes, including the evolutionarily highly conserved gene, SLC39A8 (rs13107325; C/A/T allele), and POC5 (rs2307111; T/A/C allele), as well as intronic variants in FTO (rs56094641; A/G/T allele) and NRXN3 (rs10146997; A/G allele). The discovery of the missense variants rs13107325 and rs2307111 in SLC39A8 and POC5, respectively, in addition to other intronic and synonymous SNPs suggests that these SNPs may have some roles in the development or progression of asthma and COPD. This may contribute to the identification of molecular signatures or biomarkers that forecast the risk, development, or therapeutic response of chronic lung diseases in persons with metabolic dysregulation, including obesity. Full article

Background: Glioblastoma, the most common malignant primary brain tumor in adults, continues to present a major therapeutic challenge, with a median survival of only 12–15 months and a 5-year survival rate below 2%. Despite aggressive treatment—including maximal surgical excision, radiation, and temozolomide (TMZ) chemotherapy—recurrent disease is nearly universal due to the tumor’s infiltrative nature. Objectives: To address the critical need for improved diagnostic and therapeutic strategies for glioblastoma multiforme (GBM), we have developed an innovative theranostic molecule, [^99mTc]Tc-AGT-7. Methods: AGT-7 integrates diagnostic and therapeutic modalities comprising [^99mTc]Tc-TF (a nuclear medicine imaging agent) and TMZ. The diagnostic component has been tailored to selectively accumulate in glioma mitochondria. A chelating moiety enables radiolabeling with technetium-99m (^99mTc) for precise Single-Photon Emission Computed Tomography (SPECT) imaging. The therapeutic arm includes the tethering of a TMZ moiety for localized cytotoxicity. Conclusions: In vitro studies illustrated that AGT-7 has potent cytotoxic effects in GBM cell lines (T98 and U87), with greater efficacy than TMZ, and toxicity assays in zebrafish embryos indicated a favorable safety profile. Biodistribution studies in CFW mice demonstrated that [^99mTc]Tc-AGT-7 exhibited a ~10-fold lower heart uptake compared to [^99mTc]Tc-TF, implying reduced off-target cardiac localization. This significantly lowers the risk of cardiotoxicity and enhances AGT-7’s potential as a glioma-targeted theranostic agent. Full article

Background: The renin–angiotensin system (RAS) is pivotal in regulating cardiovascular function, while cardio-genomics offers insights into genetic factors influencing cardiovascular disease (CVD) susceptibility. Aim: This study investigates the relationship between the angiotensin-converting enzyme insertion/deletion variant (ACE I/D) and the angiotensinogen gene M235T variant (AGT M235T) in Mediterranean, North African, and Middle Eastern populations. Methods: A systematic review and meta-analysis, encompassing studies until December 2023, were conducted utilizing the PubMed and Scopus databases. The study followed the PICO checklist to enroll in the review process. The meta-analysis results were obtained using CMA software V2. Results: An analysis of 12 studies (2984 participants) for ACE I/D and 7 studies (2275 participants) for AGT M235T revealed significant associations between these gene variants and increased CVD risk in Mediterranean and North African populations. Conclusions: These findings underscore the utility of cardio-genomics in delineating CVD susceptibility among these groups, emphasizing targeted interventions and personalized treatment strategies Full article

The venom of Nemopilema nomurai jellyfish represents a promising source of bioactive compounds with potential pharmacological applications. In our previous work, we identified two novel angiotensin-converting enzyme (ACE)-inhibitory peptides—IVGRPLANG (896.48 Da) and IGDEPRHQYL (1227.65 Da)—isolated from N. nomurai venom hydrolysates via papain digestion. In this study, we conducted a detailed biochemical and computational characterization of these peptides. The IC₅₀ values were determined to be 23.81 µM for IVGRPLANG and 5.68 µM for IGDEPRHQYL. Kinetic analysis using Lineweaver–Burk plots revealed that both peptides act as competitive ACE inhibitors, with calculated inhibition constants (K_i) of 51.38 µM and 5.45 µM, respectively. To assess the structural stability of the ACE–peptide complexes, molecular dynamics simulations were performed. Root mean square deviation (RMSD) and root mean square fluctuation (RMSF) analyses provided insights into complex stability, while interaction fraction analysis elucidated key bond types and residue–ligand contacts involved in binding. Furthermore, a network pharmacology approach was employed to predict therapeutic targets within the renin–angiotensin–aldosterone system (RAAS). Eleven target proteins were identified: IVGRPLANG was associated with REN, ACE, CTSB, CTSS, and AGTR2; IGDEPRHQYL was linked to REN, AGT, AGTR1, AGTR2, KNG1, and BDKR2. Molecular docking analyses using HADDOCK software (version 2.4) were conducted for all targets to evaluate binding affinities, providing further insight into the peptides’ therapeutic potential. Full article